Beta-lactam antibiotics are the most widely used group of antibiotics in the treatment of infections caused by both Gram-positive and Gram-negative bacteria. Antibiotherapies with beta-lactam antibiotics via the so-called “continuous infusion” method is more and more required in hospitals due to the increasing occurrence of complicated infections and bacterial resistances. This is particularly true for patients in services of intensive care, services of orthopedic surgery and pediatric services. For best optimization of the dosing of beta-lactam antibiotics during antibiotherapy, whether by continuous infusion or conventional administration, continuous monitoring and adjustment of the amount delivered to the patient is required. Therefore, it is of paramount importance to be able to rapidly and continuously quantify the concentration of free beta-lactam antibiotics circulating in the patient's blood during antibiotherapy.
In the medical field, the quantitative analysis of beta-lactam antibiotics is performed in clinical laboratories, using mainly microbiological or biochemical (HPLC) assays. Microbiological analyses have the disadvantage that they last a few days and thus rapid follow up of the delivered drug doses is impossible.
In the agro-alimentary field, several methods have been developed for the quantitative analysis of beta-lactam antibiotics, in particular for the quality control of milk. Some of these methods make use of radioactive labeling and disadvantageously require therefore special equipment. Furthermore, these procedures are not without danger for the person performing the analysis. Alternative methods have been described for the quantitative analysis of beta-lactam antibiotics without radioactive labeling; however, these methods do not cover the detection of some important beta-lactam antibiotics used in the medical field. Furthermore, methods have been developed for the detection of beta-lactam antibiotics in milk which make use of a device on which a reference antibiotic is immobilized. The device comprises a solid support whereon several membranes are fixed. Such methods however do not allow the continuous monitoring of beta-lactam antibiotics required during antibiotherapy.
Unfortunately, the concentration of free beta-lactam antibiotics in serum cannot be predicted from the drug doses delivered to the patient. Indeed, serum concentrations of free beta-lactam antibiotics feature great differences and variations from one patient to another, since serious infections are characterized by important disorders in drug distribution and elimination parameters, and in serum protein rates. Consequently, the optimal delivery of beta-lactam antibiotics remains often restricted to a few advanced hospital services because of the difficulty to get rapid measurements of free beta-lactam antibiotics in serum.
Accordingly, a need exists to develop further and improved methods for the quantification of beta-lactam antibiotics in samples, such as complex physiological samples.